Imlygic

Handling

Healthcare providers who are immunocompromised or pregnant should not prepare or administer talimogene laherparepvec and should not come into direct contact with the injection sites, dressings, or body fluids of treated patients

Avoid accidental exposure and follow universal biohazard precautions for preparation, administration, handling, and disposal

Preparation

Thawing

• Determine total volume required for injection (up to 4 mL)
• Thaw frozen vials at room temperature (20-25ºC [68-77ºF]) until liquid (~30 minutes)
• Do not expose the vial to higher temperatures
• Keep the vial in original carton during thawing
• Swirl gently; do NOT shake
• After thawing, administer immediately or store refrigerated (see Storage)

Prepare syringes

• Prepare sterile syringes and needles
• A detachable needle of 18-26 gauge may be used for withdrawal and a detachable needle of 22-26 gauge may be used for injection
• Small-unit syringes (eg, 0.5-mL insulin syringes) are recommended for better injection control
• Using aseptic technique, remove the vial cap and withdraw the product from the vial into the syringe(s), noting the total volume
• Avoid generating aerosols when loading syringes with product, and use a biologic safety cabinet if available

Intralesional Administration

For intralesional injection only; do not administer IV

Administer by injection into cutaneous, subcutaneous, and/or nodal lesions that are visible, palpable, or detectable by ultrasound guidance

Preinjection preparation

• Clean the lesion and surrounding areas with an alcohol swab and let dry
• Treat the injection site with a topical or local anesthetic agent, if necessary
• Do not inject anesthetic agent directly into the lesion
• Inject anesthetic agent around the periphery of the lesion

Injection

• Inject intralesionally into cutaneous, subcutaneous, and/or nodal lesions that are visible, palpable, or detectable by ultrasound guidance
• Using a single insertion point, inject solution along multiple tracks as far as the radial reach of the needle allows within the lesion to achieve even and complete dispersion
• Multiple insertion points may be used if a lesion is larger than the radial reach of the needle
• Inject evenly and completely within the lesion by pulling the needle back without exiting the lesion
• Redirect the needle as many times as necessary while injecting the remainder of the dose
• Continue until the full dose is evenly and completely dispersed
• When removing the needle, withdraw it from the lesion slowly to avoid leakage of solution at the insertion point
• Repeat preinjection preparation and the above injection procedure for other lesions to be injected
• Use a new needle any time the needle is completely removed from a lesion and each time a different lesion is injected

Postinjection

• Apply pressure to the injection site(s) with sterile gauze for at least 30 seconds
• Swab the injection site(s) and surrounding area with alcohol
• Change gloves and cover the injected lesion(s) with an absorbent pad and dry occlusive dressing
• Wipe the exterior of occlusive dressing with alcohol
• Advise patients to keep the injection site(s) covered for at least the first week after each treatment visit or longer if the injection site is weeping or oozing
• Instruct patients to replace the dressing if it falls off
• The patient should avoid touching or scratching the injection sites or the occlusive dressing as it may lead to inadvertent transfer of injection solution to other parts of the body

Storage

Store and transport frozen at -90°C to -70°C (-130°F to -94°F)

Protect from light

Store frozen in the carton until use

Thaw immediately prior to administration (see Preparation)

Do not draw thawed solution into a syringe until immediately prior to administration

Thawed vials

• After thawing at room temperature (see Preparation), administer immediately or store in its original vial and carton, protected from light in a refrigerator (2-8°C [36° to 46°F])
• Do not refreeze after thawing
• Discard (according to chemotherapy guidelines) any vial left in the refrigerator longer than the specified times listed below
• 10^6 (1 million) PFU per mL: Do not exceed 12 hr of refrigeration storage
• 10^8 (1 million) PFU per mL: Do not exceed 48 hr of refrigeration storage

• Amgen Inc

Imlygic is part of the drug class:

• OTHER ANTINEOPLASTIC AGENTS

Serious side effects have been reported with Imlygic. See the “Imlygic Precautions” section.

Common side effects of Imlygic include the following:

• fatigue
• chills
• fever
• nausea
• flu-like symptoms
• pain at the injection site

This is not a complete list of Imlygic side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

• anti-herpes viral agents such as acyclovir, famciclovir, or valacyclovir
• steroids or other medications that suppress the immune system

This is not a complete list of Imlygic drug interactions. Ask your doctor or pharmacist for more information.

• Keep all appointments with your doctor during treatment with Imlygic.
• Follow your doctor's instructions on how to properly care for your injection sites after each treatment and prevent spreading of Imlygic to others.

Follow all directions on your medicine label and package. Tell each of your healthcare providers about all your medical conditions, allergies, and all medicines you use.

Accidental exposure to the virus in talimogene laherparepvec may cause you to develop symptoms of herpes virus infection. However, not treating melanoma can allow the cancer to progress and spread to other parts of the body. Melanoma is difficult to treat after it progresses, and this type of cancer can be fatal. Talk to your doctor about the risks and benefits of using talimogene laherparepvec.

You should not be treated with talimogene laherparepvec if you are allergic to it, or if:

• you have a weak immune system (caused by disease or by using certain medicine); or

• you are pregnant.

To make sure this medicine is safe for you, tell your doctor if you have:

• blood cancer (leukemia);

• bone marrow cancer (myeloma);

• HIV or AIDS;

• an autoimmune disorder such as rheumatoid arthritis, lupus, or psoriasis;

• a history of cold sores or genital herpes;

• if you are pregnant; or

• if you use a steroid medication (prednisone, dexamethasone, fluticasone, or others).

Tell your doctor if anyone in your household is pregnant or has a weak immune system.

This medicine can harm an unborn baby or cause birth defects. Do not use if you are pregnant, and tell your doctor right away if you become pregnant. Use effective birth control to prevent pregnancy while you are using this medicine. Follow your doctor's instructions about how long to prevent pregnancy after your treatment ends.

It is not known whether talimogene laherparepvec passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

Talimogene laherparepvec is injected directly into a tumor on your skin, or into a lymph node under your skin. A healthcare provider will give you this injection.

This medicine is usually given every 2 weeks or until your tumor is gone. The first two injections of talimogene laherparepvec are usually given 3 weeks apart.

Your care providers will use special precautions to avoid getting this medicine on other areas of your body. If this medicine accidentally gets on your skin, wash it thoroughly with soap and warm water.

The virus contained in talimogene laherparepvec is a weak form of the herpes simplex virus that can spread to other parts of your body. Carefully follow your doctor's instructions about taking care of the places on your body where this medicine is injected.

• For at least 1 week after your injection, keep the treatment area covered with an airtight and waterproof bandage. You may need to keep the treated area covered for longer than 1 week if it is draining or oozing.

• Change your dressing often, to keep the treated area clean.

• Wear latex gloves while you are cleaning the treatment area or putting on a new bandage. Place used gloves and bandages in a sealed plastic bag and throw it away in the trash.

The virus in this medicine can also spread to other people you have close contact with. Avoid being near people who are sick or have infections. Avoid kissing anyone who has a mouth sore or cold sore (sometimes called a fever blister). Also avoid being near pregnant women.

Call your doctor if you you have any new skin lesions or signs of lymph gland tumors after you have stopped using talimogene laherparepvec.

Since this medicine is given by a healthcare professional in a medical setting, an overdose is unlikely to occur.

General

Restricted Distribution Program

• Available only through specialty distributors.3 Consult the Imlygic website for specific information (http://www.imlygic.com).3

Administration

Intralesional Administration

Administer by intralesional injection into cutaneous, subcutaneous, and/or nodal lesions that are visible, palpable, or detectable by ultrasound guidance.1 Do not administer by IV injection.1

Administer using a 22- to 26-gauge needle; syringes calibrated in small increments (e.g., 0.5-mL insulin syringes) recommended for better injection control.1

Consult manufacturer’s labeling for detailed information on administration of talimogene laherparepvec.1

Prior to administration, clean lesions and surrounding areas with alcohol and allow to dry.1 May administer topical or local anesthetics prior to injection of talimogene laherparepvec; however, do not inject anesthetic agents directly into lesions.1

Inject talimogene laherparepvec using a single insertion point; multiple insertion points may be used if a lesion is larger than the radial reach of the needle.1 From the single insertion point, pull back needle without exiting the lesion and redirect along multiple tracks until the full dose has been evenly and completely dispersed within the lesion.1 Slowly withdraw needle from lesion to avoid leakage.1 Use new needle if a needle is completely withdrawn from a lesion and each time a different lesion is injected.1

Apply pressure to the injection site with sterile gauze for ≥30 seconds and clean injection site and surrounding area with alcohol.1 Change gloves and apply an absorbent pad and dry occlusive dressing over the injected lesion(s); wipe exterior of the dry occlusive dressing with alcohol.1

Frozen suspensions of talimogene laherparepvec must be completely thawed at room temperature (20–25°C) for approximately 30 minutes in the original carton prior to administration.1 Do not expose to temperatures >25°C.1 (See Storage under Stability.)

Mix the suspension by gentle swirling; do not shake.1

Withdraw appropriate volume (up to 0.1–4 mL depending on lesion size) (see Dosage under Dosage and Administration) of talimogene laherparepvec suspension into a sterile syringe with an 18- to 26-gauge needle.1 Replace with 22- to 26-gauge needle for intralesional injection.1

Avoid aerosolization of the oncolytic virus when withdrawing the suspension into the syringe.1 The manufacturer recommends preparing talimogene laherparepvec in a biologic safety cabinet.1

Administer immediately following preparation of syringe.1

Immunocompromised or pregnant health-care personnel should not handle talimogene laherparepvec or come into direct contact with talimogene laherparepvec injection sites, dressings, or body fluids of treated patients.1 (See Accidental Exposure under Cautions.)

Follow procedures for proper handling (e.g., use of gloves, protective clothing, and eyewear or face shield) and disposal of biohazard waste, including administration equipment (e.g., vial, syringe, needle, cotton gauze, gloves, masks, dressings), when preparing or administering talimogene laherparepvec.1 Cover open wounds prior to handling talimogene laherparepvec suspension.1

If accidental occupational exposure occurs (e.g., through a splash to the eyes or mucosa), flush affected area with water for ≥15 minutes.1 If contact with broken skin or a needlestick injury occurs, clean affected area with soap and water and/or a disinfectant.1

If spillage occurs, treat affected area with a virucidal agent (e.g., sodium hypochlorite 1%) and blot with absorbent materials.1

Dosage

Dosage expressed in plaque-forming units (PFU).1

Adults

Use talimogene laherparepvec 1 million (1 × 106) PFU/mL for the initial treatment visit, followed 3 weeks later by talimogene laherparepvec 100 million (1 × 108) PFU/mL; administer all subsequent doses (including reinitiation of therapy) at 2-week intervals using talimogene laherparepvec 100 million PFU/mL.1

Injection volume of talimogene laherparepvec depends on the lesion size (see Table 1), but do not exceed 4 mL per treatment visit for all lesions combined.1 If lesions are clustered together, inject the cluster as a single lesion according to the injection volumes in Table 1.1

May not be possible to treat all lesions in one treatment visit or even over the full course of treatment.1 Give highest priority to treating the largest lesion(s) at the initial treatment visit and any new lesions (i.e., lesions that developed after the previous treatment visit) at subsequent treatment visits; prioritize remaining lesions by size until the maximum injection volume has been reached or until all injectable lesions have been treated.1

Continue treatment for ≥6 months or until no injectable lesions are present.1

May reinitiate therapy if new unresectable cutaneous, subcutaneous, or nodal lesions appear after a complete response was achieved.1

Prescribing Limits

Adults

Maximum injection volume of 4 mL per treatment visit for all injected lesions combined.1

Special Populations

No special population dosage recommendations at this time.1

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Distribution of talimogene laherparepvec is restricted.3 (See Restricted Distribution Program under Dosage and Administration.)

• If you need to store Imlygic (talimogene laherparepvec) at home, talk with your doctor, nurse, or pharmacist about how to store it.

Imlygic is a genetically modified oncolytic viral therapy indicated for the local treatment of unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma recurrent after initial surgery.

Limitations of use: Imlygic has not been shown to improve overall survival or have an effect on visceral metastases.

The most commonly reported adverse drug reactions (≥ 25%) in Imlygic-treated patients were fatigue, chills, pyrexia, nausea, influenza-like illness, and injection site pain.

The following adverse reactions are discussed in greater detail in another section of the label:

• Herpetic Infection [see Warnings and Precautions (5.2)]
  
• Injection Site Complications [see Warnings and Precautions (5.3)]

      Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of Imlygic was evaluated in 419 patients who received at least 1 dose of either Imlygic (n = 292) or subcutaneously administered granulocyte-macrophage colony-stimulating factor (GM-CSF) (n = 127) in an open-label, randomized clinical study of patients with stage IIIB, IIIC, and IV melanoma that was not considered to be surgically resectable [see Clinical Studies (14)]. The median duration of exposure to Imlygic was 23 weeks (5.3 months). Twenty-six patients were exposed to Imlygic for at least 1 year.

Most adverse reactions reported were mild or moderate in severity and generally resolved within 72 hours. The most common grade 3 or higher adverse reaction was cellulitis [see Warnings and Precautions (5.3)].

Pyrexia, chills, and influenza-like illness can occur any time during Imlygic treatment but were more frequent during the first 3 months of treatment. 

Table 4 below lists adverse reactions with a 5% or greater incidence in the Imlygic arm compared to the GM-CSF arm in the clinical study [see Clinical Studies (14)].

Other adverse reactions associated with Imlygic in the open-label, randomized study include rash, dermatitis, glomerulonephritis, vitiligo, worsening psoriasis, cellulitis, pneumonitis, vasculitis, herpetic keratitis, obstructive airway disorder, plasmacytoma at the injection site, deep vein thrombosis, and oral herpes.

Imlygic (talimogene laherparepvec) is a sterile suspension for intralesional injection. Imlygic is a live, attenuated HSV-1 that has been genetically modified to express huGM-CSF. The parental virus for Imlygic was a primary isolate, which was subsequently altered using recombinant methods to result in gene deletions and insertions.

Each vial contains 1 mL deliverable volume of Imlygic at either 1 x 106 (1 million) PFU per mL or 1 x 108 (100 million) PFU per mL concentrations and the following excipients: di-sodium hydrogen phosphate dihydrate (15.4 mg), sodium dihydrogen phosphate dihydrate (2.44 mg), sodium chloride (8.5 mg), myo-inositol (40 mg), sorbitol (20 mg), and water for injection.

The 106 (1 million) PFU per mL vial of Imlygic contains a clear to semi-translucent liquid following thaw from its frozen state. The 108 (100 million) PFU per mL vial of Imlygic contains a semi-translucent to opaque liquid following thaw from its frozen state. The liquid in each vial may contain white, visible, variously shaped, virus-containing particles. 

Each vial of Imlygic may also contain residual components of VERO cells including DNA and protein and trace quantities of fetal bovine serum.

The product contains no preservative.

Imlygic (talimogene laherparepvec) is a cancer medicine that affects the actions of the body's immune system, helping the body produce an "antitumor" response.

Imlygic is a genetically modified weak form of type 1 herpes simplex virus (the virus that causes common cold sores).

Imlygic is used to treat a type of cancer called melanoma when it is on the skin or in the lymph glands.

Usual Adult Dose of Imlygic for Melanoma - Metastatic:

Initial Dose:
-Up to 4 mL at a concentration of 10(6) [1 million] plaque-forming units (PFU) per mL by intralesional injection.
-Largest lesion(s) should be injected first.
-Remaining lesion(s) should be prioritized for injection based on lesion size.

Second Dose:
-Up to 4 mL at a concentration of 10(8) [100 million] PFU per mL by intralesional injection 3 weeks after initial treatment.
-New lesions that developed since initial treatment should be injected first.
-Remaining lesion(s) should be prioritized for injection based on lesion size.

All Subsequent Treatments (including Reinitiation):
-Up to 4 mL at a concentration of 10(8) [100 million] PFU per mL by intralesional injection 2 weeks after previous treatment.
-New lesions that developed since previous treatment should be injected first.
-Remaining lesion(s) should be prioritized for injection based on lesion size.

Maximum Dose: The total injection volume for each treatment visit should not exceed 4 mL for all injected lesions combined.

Duration of Therapy:
-At each treatment visit: Lesions should be injected until maximum injection volume is reached or until all injectable lesion(s) have been treated.
-Full treatment course: At least 6 months unless other treatment is required or until there are no injectable lesions to treat.

Comments:
The injection volume should be based on lesion size (lesions clustered together should be treated as a single lesion):
-Greater than 5 cm: Up to 4 mL
-Greater than 2.5 cm to 5 cm: Up to 2 mL
-Greater than 1.5 cm to 2.5 cm: Up to 1 mL
-Greater than 0.5 cm to 1.5 cm: Up to 0.5 mL
-0.5 cm or less: Up to 0.1 mL

Use: Local treatment of unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma recurrent after initial surgery.